The study aimed to explore and describe the experiences of people treated for multidrug resistant tuberculosis (MDR-TB) in Omaheke region, Namibia in order to make relevant recommendations regarding their management. A descriptive qualitative design approach was used. Data was collected using in-depth individual interviews with six participants. The interview transcripts were analysed using thematic content analysis. Three themes emerged namely (1) Stressors related to MDR-TB diagnosis and treatment which involved nature of disease and compulsory hospitalisation (2) Impact of being treated for MDR-TB which related to emotional , social , spiritual and financial impact (3) Support structures for people treated for MDR-TB which included family members, health care professionals and friends. Systemic practical patient-centred, staff-centred and community-centred recommendations are suggested as well as recommendations for future research and an appraisal of the limitations of this study. / Health Studies / M.A. (Public Health)

Over the last few years the World Health Organization (WHO) has endorsed several tests for the rapid detection of multidrug-resistant tuberculosis (MDR-TB) in resource-poor settings. The objective of this study was to compare the cost-effectiveness of a line probe assay test (less than one week for results) to conventional (bacterial culture) drug susceptibility testing (one month for results) for the detection of MDR-TB in an HIV-positive South African population by estimating the incremental cost-effectiveness ratio (ICER) per disability-adjusted life-year (DALY) averted. Costs of testing, drug treatment, hospitalization, as well as estimates for mortality, treatment success, and failure rates were obtained from literature sources, the South African Department of Health, the WHO, the Foundation of Innovative Diagnostics (FIND), and expert opinion. The willingness-to-pay threshold for a DALY averted was pre-set at 3 times the 2009 GDP per capita (about $17,400) for South Africa. In the base-case scenario for a prevalence of 30% of MDR-TB among HIV-positive patients, the average cost per person for the line probe assay testing strategy was $3,539/0.458 DALY averted and the conventional testing approach was $3,011/0.430 DALY averted. The base-line ICER was about $18,800 per DALY averted – about $1,400 above the pre-set threshold. In sensitivity analyses, the model was robust to changes in prevalence (+ 50%); costs (+ 10%), and probabilities of death, success and failure (+ 20%). However, when the treatment success rate for the line probe assay test was increased to 60% (one of the targets set by WHO in TB treatment) the ICER was below the willingness-to-pay level (i.e., cost-effective). The probabilistic sensitivity analysis showed there is a 70% chance that the additional cost of the line probe assay, compared with conventional testing, was less than $30,000 per DALY averted. However, the model may have underestimated the benefits of the line probe assay because it did not account for a decrease in the transmission of the disease due to earlier treatment nor did it measure any benefits more than a year after testing. / text

The study aimed to explore and describe the experiences of people treated for multidrug resistant tuberculosis (MDR-TB) in Omaheke region, Namibia in order to make relevant recommendations regarding their management. A descriptive qualitative design approach was used. Data was collected using in-depth individual interviews with six participants. The interview transcripts were analysed using thematic content analysis. Three themes emerged namely (1) Stressors related to MDR-TB diagnosis and treatment which involved nature of disease and compulsory hospitalisation (2) Impact of being treated for MDR-TB which related to emotional , social , spiritual and financial impact (3) Support structures for people treated for MDR-TB which included family members, health care professionals and friends. Systemic practical patient-centred, staff-centred and community-centred recommendations are suggested as well as recommendations for future research and an appraisal of the limitations of this study. / Health Studies / M.A. (Public Health)

Master of Public Health - MPH / Decentralisation of multi-drug resistant tuberculosis (MDR-TB) services has resulted in improved access to care, with community-based treatment of MDR-TB shown to be more effective than centralised hospital-based care. Furthermore, increasing bed shortages resulted in the National Department of Health establishing MDR-TB policy guidelines in 2011. However, the extent to which this policy has been implemented by the decentralised MDR- TB sites and the factors influencing implementation of the policy from a management perspective were not well described. The aim of this study was therefore to explore and compare the actual and ascribed roles and responsibilities of key management-level role players at the decentralised MDR-TB sites, and to explore the factors influencing implementation of the MDR-TB decentralisation policy (2011).

Magister Scientiae (Occupational Therapy) - MSc(OT) / TB is a multi- faceted public health problem spurred on by the biological progression of the disease as well as the social issues associated with it. The treatment of TB is however primarily driven by the medical model where the focus is on the disease and not on a holistic view of the patient. Occupational therapy is a profession concerned with the use of occupation in the promotion of health and well being through the facilitation of the process of occupational adaptation. There is however a paucity of literature pertaining to the role that occupational therapy could play within the TB context. The aim of this study was to explore how adults with MDR- TB who undergo long-term hospitalisation at a hospital in the Western Cape experience occupational adaptation. The objectives of the study were to explore how the participants perceive their occupational identity, to explore the meaning and purpose the participants assign to their occupational engagement and to explore the how the participants perceive their occupational competence. The interpretive research paradigm employing a phenomenological qualitative research approach was utilized in this study. Purposive sampling was used to select four participants based on specific selection criteria. The data gathering methods utilized included diaries, semistructured interviews, participant observation and a focus group. Photographs taken by the researcher for the purpose of participant observation were used to elicit a rich, in depth response from the participants during the focus group discussion. All data was analysed through thematic content analysis. The study findings highlighted that the participants viewed themselves as occupational beings and that they valued the role that occupational engagement played in facilitating their occupational competence and ultimately their ability to adapt to long- term hospitalisation. The environmental demands and constraints that they experienced however infringed their engagement in meaningful occupation and hampered their ability to achieve occupational competence. It was recommended that the hospital adopt an integrative intervention approach to the management of MDR- TB patients that include principles of psychosocial rehabilitation and occupational enrichment to address occupational risk factors and institutionalisation.

BACKGROUND: Multi drug resistant Tuberculosis (MDR-TB) is a serious public health concern in many parts of the world. As per the WHO- 2010 global report on Surveillance and response 3.6% of all incident TB cases globally are multidrug resistant. In this regard, there is an increasing demand for timely, reliable and comprehensive drug susceptibility testing (DST) as MDR-TB surveillance is being geared up. The intent of this analysis is to determine whether there is a need to continue routine confirmatory DST testing at CDC in addition to just sending the isolates for genotyping. Analysis is done by measuring the discordance between the results of laboratory DST at CDC and the local labs drug type, drug testing concentrations, and study sites. METHODS: The data for this analysis was provided by the Tuberculosis Trials Consortium (TBTC), CDC. Data for this analysis was collected over nearly two decades (1993-2011), gathered from 7 clinical trials. Discordance between the local and CDC lab DST results was measured using Kappa statistic. Sensitivity and specificity analysis was done by taking the CDC DST lab results as the gold standard. Discordance levels were calculated by local sites and baseline drug resistance for each antibiotic in each study was measured. RESULTS: Average Kappa values for inter rater agreement for all the studies was 0.6444 whereas the overall level of discordance across all studies is 7.786%. Drug resistance at baseline was highest for Isoniazid and Streptomycin (except Study 23 and 22). CONCLUSION: Though the current results show few DST result discordances between local and CDC labs, it is better to continue to send isolates to the centralized lab (CDC) in view of the worldwide threat of drug resistant TB epidemic, the recommendations of the current literature and the benefits of reliable confirmatory testing services and availability of other molecular diagnostic methods.

Magister Pharmaceuticae - MPharm / Tuberculosis and HIV are arguably South Africa’s largest and most important health issues. With drug-resistant strains of tuberculosis on the increase and little research on new drugs, there is an urgent need for research around the drugs presently available to ensure their optimal use and to minimise their sometimes serious and significant side effects. Treatment of drug-resistant tuberculosis is expensive and lengthy, and is complicated by a limited choice of drugs with lower efficacies and higher toxicities. Treatment is further complicated in patients with HIV due to several factors including drug interactions. While some authors suggest that HIV and malabsorption might be associated with poor clinical outcomes, other researchers have found no link. Patients may benefit from Therapeutic Drug Monitoring in order to ensure that their doses of antituberculosis drugs are reaching the required minimum effective concentrations, without attaining toxic levels in the plasma which may cause unpleasant side effects. There is little research concerning drug levels in HIV patients with TB in South Africa, let alone in patients with drug-resistant forms of tuberculosis, and there are no studies in this country that use Liquid Chromatography-Mass Spectrometry to investigate the plasma levels of pyrazinamide in patients with MDR-TB. This study aimed to investigate whether or not there is a difference in the pharmacokinetics of PZA in MDR-TB patients with HIV, and those without HIV infection. It also aimed to establish whether LC-MS could be used to study the levels of pyrazinamide in the plasma of patients with multidrug-resistant tuberculosis with and without concurrent HIV infection. The plasma levels of pyrazinamide in 32 MDR-TB patients (23 HIV negative and 9 HIV positive), were successfully 2 analysed using LC-MS, and the pharmacokinetics of PZA in these 2 populations was described. It was established that the Tmax of pyrazinamide was significantly higher in HIV-negative patients than in HIV-positive patients. Although there was a difference between the Ka in the two populations, this difference did not quite reach statistical significance. There were no statistically significant differences between HIV-negative and HIV-positive patients with regards to the other pharmacokinetic parameters investigated. Our findings established that there was little evidence to suggest that there is a difference between the pharmacokinetics of the antimycobacterial drug pyrazinamide in HIV-positive patients and that in HIV-negative patients. We were also able to successfully develop and validate an assay for the analysis of PZA in plasma using LC-MS, and this finding could be very valuable for further studies. Although our study failed to prove this, the possibility still exists that HIV-positive patients could exhibit altered kinetics of antiTB drugs and this has not been fully investigated in South Africa. The clinical impact of low plasma levels of antimycobacterial drugs is still largely unexplored and further research with larger sample sizes should be done in order to establish which factors may contribute to low plasma levels of anti-tuberculosis drugs in MDR-TB patients, and whether or not these low levels are increasing the risk of treatment failure or other poor clinical outcomes.

Thesis (MSc. (Medical Sciences)) -- University of Limpopo, 2015 / Introduction: Multidrug-resistant tuberculosis (MDR-TB) caused by resistance to at least rifampicin (RIF) and isoniazid (INH) drugs is a growing public health concern in South Africa. The detection of MDR-TB still relies on culture despite advancement in molecular diagnostic technology. Currently MTBDRplus and GeneXpert are the only available assays used in rapid diagnosis of MDR-TB using chromosomal mutations in drug target regions. Some strains are missed by these assays due to their limitation in mutational detection profile. Novel Seegene Anyplex assays simultaneously detect TB and resistance to RIF and INH using fifteen and six mutational probes, respectively within 3 hours. Limpopo Province has limited information on the circulating strains of TB. Aim: To determine drug-resistant Mycobacterium tuberculosis (M. tuberculosis) mutations using Anyplex™ MTB/NTM/MDR-TB real time assay and characterise the drug-resistant strains. Methods: We prospectively collected 204 clinical samples at Modimolle MDR-TB unit and retrospectively used 104 culture isolates from MRC laboratory in Pretoria. The MTBDRplus assay was used to screen for M. tuberculosis and drug resistant mutations to RIF and INH drugs. Anyplex™ MTB/NTM/MDR-TB assay was used for rapid detection of M. tuberculosis and drug resistance to RIF and INH within 3 hours. The discordance between phenotypic and genotypic assays was resolved by sequencing and the Anyplex™ resistant profiles were spoligotyped. Diagnostic data was collected from NHLS and MRC databases and analysed using the Microsoft excel and Epi Info version 3.5. Descriptive statistics (percentages and frequencies) were used to explain proportions. Results: The Anyplex™ MTB/NTM assay detected M. tuberculosis in 69/111(62%) and 100/104 (96%) of clinical and culture samples respectively. The sensitivities, specificity, PPV and NPV obtained for both RIF and INH resistance by Anyplex™ MDR-TB assay were 67%, 59%, 67%, 55% and 15%, 100%, 100% and 17%, respectively. Anyplex™ MTB/NTM/MDR-TB resolved 23/45 (51%) of discordant vi samples. Sequencing of remaining discordant isolates revealed L511P, L533P and D516Y mutations within rpoB gene. A novel R385W mutation within katG was also detected. Spoligotyping of Anyplex™ MDR-TB resistant clinical isolates revealed Euro American clade with 20% followed by 15% Manu2, 5% East African Indian, 5% H37Rv, 5% atypical and 50% were orphans. Conclusion: The novel Anyplex™ MTB/NTM/MDR-TB assay is a rapid and valid technique for detecting M. tuberculosis and most common mutations conferring resistance to RIF and INH. However further investigations are required, as the assay has a lower sensitivity as compared to already endorsed techniques. / National Research Foundation (NRF) and University of Limpopo TB Grant

Philosophiae Doctor - PhD / Although TB is a curable communicable disease, poor adherence to TB treatment is a major barrier to TB control in South Africa as it increases the risks of morbidity, mortality and drug resistance at individual and community level. As a result, multi-drug-resistant TB (MDR-TB) has become a serious public health issue. Underpinning this study was the assumption that a client-centred approach to treatment of MDR-TB clients, with a hospital programme which adopts an integrated multidisciplinary approach that is client-centred and is not purely biomedically driven, would improve treatment outcomes of MDR-TB clients.

This quantitative, descriptive study investigated factors that contributed to TB patients registered in four Tembisa clinics in 2001, defaulting treatment. An interview schedule with closed and open-ended questions was used for 30 patients who could be traced who had interrupted treatment. The reasons for treatment interruption were related to socio-economic, TB policy-related and health care worker-related factors. The findings illustrate that TB management requires a multi-sectoral approach and joint efforts to tackle the disease that continues to kill people even though it is curable. / Health Studies / M.A. (Health Studies)